Chrysin–phospholipid complex-based solid dispersion for improved anti-aging and neuroprotective effects in mice

Abstract

The present study aimed to improve the neuroprotective effect of chrysin (CHR) by combining two formulation techniques, phospholipid (PL) complexation and solid dispersion (SD). CHR-phospholipid complex (CHR-PLC) was prepared through solvent evaporation. The molar ratio CHR/PL (1:3), which exhibited the highest complexation efficiency, was selected for the preparation of CHR-PLC loaded SD (CHR-PLC-SD) with 2-hydroxypropyl β cyclodextrin (2-HPβCD) and polyvinylpyrrolidone 8000. CHR-PLC/2-HPβCD (1:2, w/w) displayed the highest aqueous solubility of CHR (5.86 times more than that of plain CHR). CHR-SD was also prepared using 2-HPβCD for comparison. The in vitro dissolution of CHR-PLC-SD4 revealed an enhancement in the dissolution rate over CHR-PLC (1:3), CHR-SD, and plain CHR by six times. The optimum formulations and plain CHR were evaluated for their neuroprotective effect on brain aging induced by D-galactose in mice. The results demonstrated a behavioral activity elevation, an increase of AMPK, LKB1, and PGC1α brain contents as well as a reduction of AGEs, GFAP, NT-3, TNF-α, and NF-κβ brain contents when compared with those of the D-galactose control group. Thus, the developed formulations stimulated neurogenesis and mitochondrial biogenesis as well as suppressed neuroinflammation and neurodegeneration. The order of activity was as follows: CHR-PLC-SD4 > CHR-PLC (1:3) > CHR-SD > plain CHR.

Graphical abstract

Keywords:

• Chrysin
• phospholipid complex
• solid dispersion
• aging
• neurogenesis

Acknowledgements

The authors would like to thank the Project’s Sector at the National Research Centre, Cairo, Egypt for funding this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors would like to thank the Project’s Sector at the National Research Centre, Cairo, Egypt for funding this work through the research project fund number: E120505.